I recently finished re-reading Microbe Hunters, a book published in 1926 to great acclaim. It’s a chatty and fascinating history of the men (and some of their assisting wives) who were at the forefront of discovering the germs that cause anthrax, malaria, syphilis, and other scourges. For reasons that are not clear to me, I was required to read this book in 1958, when I was in the 6^th grade.

Before I get to telling you about Walter Reed (one of its fascinating stories), you might wonder why anybody would choose to re-read a book about science from 1926? So here’s how that happened:

I belong to a book club (doesn’t everybody?). In this book club we recently read Stephanie Dray’s Becoming Madame Secretary, a fictional “autobiography” of Francis Perkins, a remarkable woman who became the first woman to hold a cabinet post. She was FDR’s Secretary of Labor and the prime mover behind Social Security. Anyway, in her 20’s, she was courted by Sinclair Lewis who was several years younger than she. How many of us remember that Sinclair Lewis was the first American author to win a Nobel Prize? Well, that’s all the book club needed. We simply had to read something by Sinclair Lewis and chose Arrowsmith, published in 1925.

Arrowsmith follows the career of Martin Arrowsmith, a Midwesterner who goes to medical school at the fictional University of Winnemac. While there he meets one professor Gottlieb. Skeptical of the commercialism of the medical profession, Gottlieb is driven instead by his dedication to pure research in the service of Science. Arrowsmith becomes an acolyte and subsequently spends a great deal of his career frustrated by the practice of medicine and longing to follow in Gottlieb’s footsteps. Later in his career, he gets that opportunity and discovers a potential cure for a deadly tropical disease. He is sent to the tropics where an outbreak of this scourge has occurred. Upon arrival, he is confronted with a scientific dilemma: He can either treat everyone who has the disease with his “cure,” or he can scientifically test his phage by treating one group of victims and leaving a second group untreated. If more people in the treatment group survive than in the untreated group, then and only then will he really know if his treatment is successful. No spoilers here; I won’t tell you what he decides.

What is particularly interesting about the novel is that Lewis had an essential collaborator, Paul de Kruif, a somewhat cantankerous microbiologist (he was thrown out of Rockefeller Institute after writing highly unflattering things about his colleagues). Arrowsmith’s early years mirror those of de Kruif, and Lewis would not have been able to accurately describe laboratories and experiments without de Kruif’s help. As a result, de Kruif enjoyed 25% of the royalties from the book.

When I subsequently learned that de Kruif was the author of Microbe Hunters, well, nothing would do except that I had to re-read it. And so I did. So, after learning about Leeuwenhoek and Pasteur and Koch and a few others that, to me at least, were unknown, we came to Walter Reed. So from Frances Perkins to Walter Reed, we come to the intersection of Arrowsmith and Reed.

Major Walter Reed was sent to Cuba in 1900 as the head of a four-man commission with orders to eradicate yellow fever which was, at the time, killing almost a third of U.S. troops stationed there. Reed was a doctor, but not much of a microbe hunter (yet), and he was flying blind; he and everyone else knew almost nothing about the disease.

First order of business, then, was to identify the microbe. He and his three colleagues set about to examine the blood and organs of those who died of the disease and managed to find…nothing.* At his wits’ end, Reed consulted Dr. Carlos Finlay (aka “Theorizing Old Fool”) who had proclaimed, without much (or any) evidence, that yellow fever, like malaria, was caused by a mosquito. Since they had nothing else to go on, they decided to examine his theory.

There was one catch: it was not possible to give yellow fever to any animal…except the human animal. So Reed was faced with the prospect of taking mosquitoes who had bitten sick humans and allowing those mosquitoes to bite perfectly healthy humans to see if they got sick. Having no permission from the military to perform this experiment, he nevertheless asked for volunteers. Two of his colleagues, one with a wife and five children (!), volunteered.

And so, the experiment proceeded. Both volunteers allowed mosquitoes swollen with the blood from severe cases of yellow fever to bite them. Two days later they were sick with yellow fever. To Reed’s relief, his colleagues recovered, and, importantly, he had a suggestion that mosquitoes carry yellow fever. But what if his two colleagues had caught the disease accidentally from another source before they had been bitten? Reed needed better proof. For that he needed more volunteers…paid volunteers. Soldiers volunteered (with a $300 incentive), but so did others — recently arriving Spanish immigrants who volunteered not because of their eagerness to serve humanity but simply because they needed the money.

Those to be bitten were quarantined for weeks so that there would be no chance of accidentally acquiring the disease through other means. At the end of their sequestration, they were bitten by mosquitoes who had feasted on fatal cases. All seven of them got sick. Happily, all seven survived. Reed now had very good evidence that mosquitoes transmitted the disease.

Yes, but everybody said that the disease was transmitted by the infected bedding of sick people. What about that? And so they did a truly nasty experiment. They built a house: “no draft could blow through that little house. Then it was furnished with a nice stove, to keep the temperature well above ninety…it was an uninhabitable little house…but now…sweating soldiers carried several tightly nailed suspicious-looking boxes, that came from the yellow fever wards…to make this house altogether cursed.” The boxes contained pillows, blankets, and sheets, even pajamas, from the beds of men dead of yellow fever. Three men lived in that horrid house for 20 nights! And then another three men spent 20 nights. And then another group of three. But no one got yellow fever.

Yes, but what if all of those nine men where immune to yellow fever? And so they allowed two of the men to be bitten by yellow-fever-carrying mosquitoes. Both got sick but survived to receive their $300 reward.

One last experiment: A horridly filthy house without mosquitoes did not yield yellow fever. But what about a perfectly sterile house with mosquitoes? And so it was done. Another little house, pristinely clean with disinfected everything was prepared. But…yellow fever-carrying mosquitoes were released into it along with a volunteer. Yes, he got sick.

Reed had his proof: it was mosquitoes, not dirty linen that was the vector by which the disease was spread.

I find this story stunning. The audacity, curiosity, bravery, cleverness, patience, and, yes, nobility of the participants is, to me, extraordinary. In today’s world, it was comforting to know that such valor exists…even in the past.

*It is not surprising in hindsight that they couldn’t find the microbe. Yellow fever, we know now, is caused by a virus, too small to see in the microscopes of the day.